A Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II) (COMPASS)

Denali Therapeutics

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Mucopolysaccharidosis II

Treatments: Drug: tividenofusp alfa; Drug: idursulfase

Study type: Interventional

Funder types: Industry

Identifiers

NCT05371613

DNLI-E-0007

2021-005200-35 (EudraCT Number)

2024-510990-21-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

This is a Phase 2/3, multiregional, two-arm, double-blind, randomized, active (standard-of-care)-controlled study of the efficacy and safety of tividenofusp alfa (DNL310), an investigational central nervous system (CNS)-penetrant enzyme-replacement therapy (ERT) for mucopolysaccharidosis type II (MPS II).

Participants may also qualify to enter an open-label treatment phase with DNL310 or idursulfase based on pre-specified criteria.

Enrollment: 63 estimated patients

Sex: All

Ages: 2 to 25 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Participants aged ≥2 to <6 years (Cohort A) or ≥6 to <26 years (Cohort B)
• Confirmed diagnosis of MPS II (for Cohort A, nMPS II; for Cohort B, nnMPS II)
• Have no history of treatment with enzyme replacement therapy (ERT) OR not have received continuous ERT for 4 months prior to screening OR be on maintenance ERT and have tolerated idursulfase for a minimum of 4 months prior to screening

Key Exclusion Criteria:

• Have a documented mutation of other genes or genetic diagnosis accounting for developmental delay
• Previously received an iduronate 2-sulfatase (IDS) gene therapy or stem cell therapy
• Received any CNS-targeted MPS ERT within 6 months prior to screening
• Have a contraindication for lumbar punctures and/or magnetic resonance imaging (MRI)
• Participated in any other investigational drug study or used an investigational drug within 60 days prior to screening or intend to receive another investigational drug during the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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63 participants in 3 patient groups

Cohort A: Participants with nMPS II

Experimental group

Treatment:

Drug: idursulfase

Drug: tividenofusp alfa

Cohort B: Participants with nnMPS II

Experimental group

Treatment:

Drug: idursulfase

Drug: tividenofusp alfa

Open-label Treatment Phase

Experimental group

Description:

Participants who meet pre-specified criteria may receive DNL310 or idursulfase

Treatment:

Drug: idursulfase

Drug: tividenofusp alfa